Silicates are abundant as silicates and alumino silicates. They make up nearly all the earth's crust. Many organisms use silica as protecting or fortification material against predators, infection or extreme environmental conditions. Silica can also participate in metazoan development and may influence enzymatic reactions.
Specific bacteria, protozoa, algae and plants make certain silica structures. They use silicon anions, silicate complexes or mono silicic acid to create specific silica (polymerized) structures, which are normally used as protecting shell layer. Some sponges form spicules allowing anchoring. They make therefore a differentiated cell type producing scaffolding silicatein proteins. Diatoms which are important in the biogenic silicon cycle form silicate frustules as protecting layer against predators.
Silicon is found in plants at concentrations ranging from 0.01 to 10% or more (dry weight basis). This is much higher than most macro nutrients. Multiple studies demonstrated the role of silicon as an alleviator of biotic and abiotic stress induced by other organisms (bacteria, fungi, viruses, protozoa, insects, . . . ) and s physical conditions (salt stress, drought stress, water stress, heat stress, osmotic stress, cold stress, etc . . . ). Different parts of the plant may show large variations in silicon uptake. Silica phytoliths are observed in the cell walls or lumina of plant cells. There are also associations visible with cell wall components (polysaccharides, pectins, lignins, proteins, etc . . . ). Non polymerized silica as mono and disilicic acid, the precursors of biogenic silica, may also play an active role in certain enzymatic systems involved in oxidative stress and in the biosynthesis and metabolism of certain macro molecules important in biochemical pathways (ref. 22, 23).
Humans are continuously exposed to different sources of silicon as dust (silica, silicates), soil particles (silicates, silica) dissolved silica in water, health products, inert silicon dioxide in pharmaceuticals and cosmetics, organic silicon compounds in medical implants and devices, dietary additives (inert silicates), dietary supplements (colloidal gels, dissoluble organic silicon compounds), plant extracts (phytolytic), cosmetics and toiletries (insoluble silicates), detergents, etc. Typically none of these products are highly bio-available. Only dissoluble silica and mono or disilicic acid in drinking water and in food or dietary supplements are bio-available and safe for human. Most silicon compounds are taken up by diet and drinking water. The dietary intake in a Western diet is about 15-60 mg Si/day. Higher consumption of plants results in a higher intake up to 200 mg Si/day. Beer also is an interesting source of bio available silicon.
The gastro intestinal absorption of silicon depends mainly on the presence of absorbable species of silicic acid and silicates. Only soluble silicates (or silicate complexes) and mono- or disilicic acid from dissolution of silica compounds are readily absorbed and excreted.
Moreover, silicon is still a risk factor in human diseases (ref. 24, 25, 26, 27, 28). More specifically crystalline (sands) or amorphous (natural or synthetic) silica is active through macrophage activation and release of cytokines, growth factors and oxidants (ROS). Some concerns have even been expressed on a possible association between silica and esophageal cancer. It is therefore important to produce a silica sol compound which is soluble, hydrated and preferably quickly dissoluble upon dilution. Stable and purified synthetic sol particles could be harmful. Soluble silica compounds are not at all toxic. Crystalline silica may release free radicals in solution (ROS) in combination with soluble iron and may damage so directly the epithelial cell layer. It is important that the stabilizing agent is able to scavenge the ROS radicals, which are also inducing polymerization. It is therefore crucial not to use dried or evaporated silica which dissolutes very slowly.
Silicon is not yet recognized as an essential element although it is essential for specific bacteria, fungi, diatoms and plants related to survival and replication. is Silicon plays also an important role in the growth and strength of animals and humans. Silicon is strongly related to the development of connective tissue and the activity of cells present in the extra cellular matrix and could play an important therapeutic role in the maintenance and prevention or treatment of extra cellular matrix related diseases such as arteriosclerosis, arthritis, osteoarthritis, osteoporosis, skin—hair and nail diseases, reduced mineralization of bone, reduced collagen synthesis, reduced skeleton growth, joint diseases, healing of fractures, etc. . . . It is also important in detoxification of aluminum ions and other toxic metals. Several recent publications show the importance of silicon in bone health and especially in the synthesis of collagen. It is therefore important to have access to an acceptable technology and a formulation of bio available silicon for plants, animals and humans.
The following patents: U.S. Pat. Nos. 1,233,933, 3,867,304, WO02/051748, U.S. Pat. Nos. 2,356,774, 2,391,255 and 3,083,167 deal with silica sol formation in acid medium. These documents disclose silica sols stabilized by means of ionic transfer or by use of organic silicic acid complexing compounds.
Many silicic acid compositions have been proposed as silicon suppletion products for plants, animals and humans, but they deal with non colloidal silicon or with non stabilized monosilicic acid.
U.S. Pat. No. 4,037,019 discloses acidic hydrosols and process for coating therewith. Metal silicates or hydrous magnesium silicate and optionally a magnesium compound and a boron compound are mixed in acidic medium. The obtained sols are resistant for at least 15-20 minutes. This invention describes mixtures of silicate (solid powders) which are not at all soluble in acidic medium.
U.S. Pat. No. 6,335,457 describes a complex containing biologically assimilable orthosilicic acid, wherein orthosilicic acid is complexed with a polypeptide and under solid, stable and concentrated form. Alcohol is used during the synthesis of the solid form and the pH is between 1.5 and 4 during the preparation. No silicic acid colloids are disclosed.
EP-743.922 describes the preparation of ortho silicic acid (monomer) stabilized with a quaternary ammonium compound by dissolving a silicon compound in the solution containing the stabilizing agent. Silicon molar concentrations higher than 1.4 are obtained at values under pH 4. No colloidal silicon is formed. The stabilizer must always be present and cannot be omitted.
US-2006/0178268 teaches an aqueous solution containing boric acid and non-colloidal silicic acid. Boron is present during hydrolysis of the silicon compound in an acidic solution. Boric acid absorbs to the oligomers. Without the presence of a humectant at a high concentration only very low silica (up to 0.0035 mol) and boron concentrations can be obtained. Boron is needed for stabilization of non colloidal oligomers and for the much higher biological activity. Without boron and the humectants the stability is lost at higher molar silicon concentrations at pH values below 2. The small oligomers are not retained on a MW 20.000 filter or filters with higher cut off. Humectants include urea, dextran, polysorbate, glycol, sorbitol, galactose, cellulose, vegetable gum. They must be used at concentrations higher than 30% (W/V). Boron free solutions could not be obtained by this formulation.
US-2006/099276 describes a method for the preparation of silicic acid comprising extrudate, said extrudate, its use and a pharmaceutical composition comprising the said extrudate. An extrudate of stabilized silicic acid as mono silicic acid or its oligomers is proposed. These compounds are formed in the presence of quaternary ammonium compounds, amino acids or an amino acid source and mixed with a carrier. This mixture is extruded and dried before use. Mono silicic acid and oligomers up to 40 units could be present at maximum 1.25 mol Si. Pellets are the final result. 29Si NMR shows Q0 and Q1 peaks, characteristic for mono and disilicic acid.
EP-1.110.909 describes a method for preparing ortho- or mono silicic acid starting from an acid hydrolysable compound in the presence of a solvent agent in order to prevent polymerization into oligomers and colloidal silica. The solvents for stabilization are glycols, glycerol, DMSO, polysorbate 80 and polyglycols. Mono silicic acid is made in situ. The silicon concentration is in the range of 0.01 to 50% (W/V). Silicic acid remains in its monomeric form. All examples mentioned are performed with glycerol as solvent. The solvent cannot be removed anymore (high boiling temperature).
U.S. Pat. No. 2,588,389 provides processes for production of silicic acid sols in which silicic acid has a low molecular weight and not greater than the silicate used during preparation. The solution is added to an aqueous acidic solution (pH 0.5-4 or pH 1-3) containing insoluble cation-exchangers. After addition the pH may not exceed 4. After filtration the pH is about 2-3.
U.S. Pat. No. 2,392,767 relates to the production of low molecular weight silicic acid forming complexes with an organic hydrogen bonder. The bonder is extracted by means of a solvent. The pH is between 1.6 and 3.
U.S. Pat. No. 2,408,654 relates to silicic acid sols and the process for producing silicic acid together with an organic hydrogen bonding donor (ether). The pH is variable and such that the corresponding metal silicate is not formed. The original silicic acid sol has a pH of 2.
There is still a need to produce and stabilize, for longer periods, silicic acid particles in aqueous solutions, which are able to quickly dissolve into the bioavailable forms of silicon, the mono and disilicic acids, upon dilution in an aqueous environment. Such sols are also more important than mono- or di-silicic acid in detoxification reaction of heavy metals.
Silica is ubiquitous in nature. Its precursor molecules (silicate anion, mono and disilicic acid) are present in water at low concentrations. These forms are taken up by plants and all other organisms. Silica particles formed after polymerization under natural pH conditions are negatively charged and interact with all kind of cells in the environment. Very slow dissolution of these particles finally results in mono silicic acid which is taken up by the plant cells or other organisms.
It is generally accepted that polymerization of monosilicic acid occurs at pH values under 7 through formation of siloxane bonds resulting in dimers, trimers, tetramers and larger oligomers. These mostly cyclic oligomers assemble very quickly into large fibrils and form a three-dimensional open network which results by further associations in gel formation. The oligomers show Ångstrom (Å) dimensions (non colloidal) and subsequent small sols or nano-particles which assemble in nanometer and micrometer fibrils or particles before gel formation. Primary sol particles are formed after active polymerization of hundreds of oligomers (colloidal). Once sol particles are formed it is difficult to inhibit further association and polymerization of these particles into larger particles and fibril associations (micrometer sols).
The silicate anion shows different structures: linear, planar, cyclic and three dimensional. Silicon nuclear magnetic resonance (NMR) spectroscopy provides a basic method for characterizing silicate anion mixtures. It uses the relationship between the silicon atom and its neighbors, counting the number of other silicon atoms to which atom it is connected to through an oxygen atom (Q0, Q1, Q2, Q3 and Q4). Q0: monomeric (no connections) is typical for mono silicate and Q4 is typical for all atoms in the interior of polymeric colloidal silica (ref. 29, 30, 31, 32, 33, 34, 35).
Colloidal silica shows no Q0 and Q1 peaks but heterogeneous and multiple Q3 and Q4 peaks. Oligomeric structures show distinct homogeneous Q1, Q2 and Q3 peaks. The ratios between the Qs are also different in oligomeric and colloidal silicic acid. Mono acid (H4SiO4) and disilicic acid (H6Si2O7) show the same peak characteristics as the mono and disilicate ions.
Mono silicic acid is normally neutral and relatively inert to physical conditions. It may easily cross different membrane structures. Silicate complexes and silica species (negatively loaded) react more on the different mucus layers in the intestines.
There are practically no extensive studies concerning sol and gel formation from monosilicic acid and oligomers at pH values under 1, starting from solutions of inorganic or organic silicon compounds. There are a lot of studies dealing with the formation of silica sol with the intention to make different kinds of gels. Silica sol-gel experiments with different water, silicon and proton concentrations were mainly prepared to study the effect on the gelling time, pore size and characteristics of the gel. (ref. 1 to 20). It was demonstrated that at pH values below the point of zero charge (pH 2) and more specifically at pH values inferior to 1 that the gelation time decreases and sol-gels are formed quite rapidly (ref. 21). Surprisingly, the applicants discovered that only in this low pH region, nano particles of silicic acid are formed and stabilized, under specific conditions, under the form of a colloidal suspension which is stable for several days or weeks. Moreover surprisingly the applicants discovered that only this suspension could further be stabilized with aqueous stabilizers for long periods, particularly several weeks, months or years, at ambiant temperature.
Colloidal silica nano particles for industrial use are normally stabilized after purification between pH 2 and 9. At the end of the preparation stabilized concentrated (superior to 0.7 mol Si) and desalted sols are mostly proposed. The situation under pH 2 and more precisely under pH 0.9 is not fully documented. It is proposed that dimeric silicic acid forms quickly siloxane bonds resulting finally in gelation under pH 0.9 because the polymerization time decreases (rate increases) very quickly under pH 2. It is also known that the addition of salts or peroxides (H2O2 precursors of reactive oxygen species), induces polymerization.